Modeling delay of age at natural menopause with planned tissue cryopreservation and autologous transplantation

Abstract

Ovarian tissue cryopreservation has been proven to preserve fertility against gonadotoxic treatments. It has not been clear how this procedure would perform if planned for slowing ovarian aging. This study aimed to determine the feasibility of cryopreserving ovarian tissue to extend reproductive life span and delay menopause by autotransplantation near menopause. Based on the existing biological data on follicle loss rates, a stochastic model of primordial follicle wastage was developed to determine the years of delay in menopause (denoted by D) by ovarian tissue cryopreservation and transplantation near menopause. Our model accounted for (1) age at ovarian tissue harvest (21-40 years), (2) the amount of ovarian cortex harvested, (3) transplantation of harvested tissues in single vs multiple procedures (fractionation), and (4) posttransplant follicle survival (40% [conservative] vs 80% [improved] vs 100% [ideal or hypothetical]). Our model predicted that, for most women aged <40 years, ovarian tissue cryopreservation and transplantation would result in a significant delay in menopause. The advantage is greater if the follicle loss after transplant can be minimized. As an example, the delay in menopause (D) for a woman with a median ovarian reserve who cryopreserves 25% of her ovarian cortex at the age of 25 years and for whom 40% of follicles survive after transplantation would be approximately 11.8 years, but this extends to 15.5 years if the survival is 80%. As another novel finding, spreading the same amount of tissue to repetitive transplants significantly extends the benefit. For example, for the same 25-year-old woman with a median ovarian reserve, 25% cortex removal, and 40% follicle survival, fractionating the transplants to 3 or 6 procedures would result in the corresponding delay in menopause (D) of 23 or 31 years. The same conditions (3 or 6 procedures) would delay menopause as much as 47 years if posttransplant follicle survival is improved to 80% with modern approaches. An interactive Web tool was created to test all variables and the feasibility of ovarian tissue freezing and transplantation to delay ovarian aging (here). Our model predicts that with harvesting at earlier adult ages and better transplant techniques, a significant menopause postponement and, potentially, fertile life span extension can be achieved by ovarian tissue cryopreservation and transplantation in healthy women.